CtBPs promote cell survival through the maintenance of mitotic fidelity

CtBPs promote cell survival through the maintenance of mitotic fidelity

CtBPs promote cell survival through the maintenance of mitotic fidelity

CtBPs (CtBP1 and CtBP2) act in the nucleus as transcriptional corepressors and in the cytoplasm as regulators of Golgi fission. Studies in which the expression or function of CtBPs has been inhibited have independently identified roles for CtBPs in both suppressing apoptosis and promoting cell cycle progression. Here we have analyzed the consequences of ablating CtBP expression in breast cancer-derived cell lines. We find loss of CtBP expression suppresses cell proliferation through a combination of apoptosis, reduction in cell-cycle progression, and aberrations in transit through mitosis. This third phenotype includes errors in mitotic chromosome segregation that are associated with decreased association of the chromosome passenger protein aurora B with mitotic chromatin, and which are likely to be a primary cause of the pro-apoptotic and anti-proliferative effects of CtBP loss. We also show that loss of CtBP expression results in the activation of the transcription factor p53, and that loss of p53 function renders cells more susceptible to CtBP siRNA-induced apoptosis.

Abstract

CtBPs (CtBP1 and CtBP2) act in the nucleus as transcriptional corepressors and in the cytoplasm as regulators of Golgi fission. Studies in which the expression or function of CtBPs has been inhibited have independently identified roles for CtBPs in both suppressing apoptosis and promoting cell cycle progression. Here we have analyzed the consequences of ablating CtBP expression in breast cancer-derived cell lines. We find loss of CtBP expression suppresses cell proliferation through a combination of apoptosis, reduction in cell-cycle progression, and aberrations in transit through mitosis. This third phenotype includes errors in mitotic chromosome segregation that are associated with decreased association of the chromosome passenger protein aurora B with mitotic chromatin, and which are likely to be a primary cause of the pro-apoptotic and anti-proliferative effects of CtBP loss. We also show that loss of CtBP expression results in the activation of the transcription factor p53, and that loss of p53 function renders cells more susceptible to CtBP siRNA-induced apoptosis.